Background: Neurodevelopmental abnormalities in fetal alcohol spectrum disorder (FASD) are linked to brain insulin resistance and oxidative stress. However, the role of thiamine deficiency as a distinct or additive fa...Background: Neurodevelopmental abnormalities in fetal alcohol spectrum disorder (FASD) are linked to brain insulin resistance and oxidative stress. However, the role of thiamine deficiency as a distinct or additive factor in the pathogenesis of the neurodevelopmental and metabolic derangements in FASD has not been determined. Methods: Control and ethanol-exposed human PNET2 cerebellar neuronal cells and rat cerebellar slice cultures were treated with vehicle or pyrithiamine (Pyr) to assess independent and additive effects of thiamine deficiency on ethanol-mediated neurotoxicity, mitochondrial dysfunction, insulin resistance, inhibition of neuronal and glial genes, and oxidative stress. Results: Pyr treatments (0 - 200 µM) caused dose-dependent cell loss (Crystal Violet assay) and reduced mitochondrial function (MTT assay) in PNET2 neuronal cultures. Ethanol alone (100 mM) significantly reduced PNET2 neuronal viability, MTT activity, and ATP production. Over the broad dose range of Pyr treatment, ethanol significantly reduced ATP content and cell number and increased mitochondrial mass (MitoTracker Green). Ex vivo cerebellar slice culture studies revealed ethanol-induced developmental architectural disruption that was substantially worsened by Pyr. The adverse effects of ethanol were linked to increased lipid peroxidation and inhibition of asparatyl-asparaginyl-β-hydroxylase (ASPH) expression. The independent and additive effects of Pyr were associated with increased cytotoxicity, lipid peroxidation, Caspase 3 activation, and Tau accumulation. Conclusions: During development, alcohol exposure and thiamine deficiency exert distinct but overlapping molecular pathologies that ultimately impair the structure and function of cerebellar neurons. While both insults drive cell loss and mitochondrial dysfunction with increased lipid peroxidation, ethanol’s additional inhibitory effects on ASPH reflect impairments in insulin and IGF signaling. In contrast, Pyr’s main adverse effects were likely due to neurotoxicity and the activation of apoptosis cascades. The findings suggest that FASD severity may be reduced by thiamine supplementation, but without additional support for insulin/IGF signaling networks, FASD would not be prevented.展开更多
BACKGROUND Several conditions may present with acute neurological symptoms,thus mimicking the presentation of stroke.Although the underlying disorder can be diagnosed after careful medical,neurological,and radiologica...BACKGROUND Several conditions may present with acute neurological symptoms,thus mimicking the presentation of stroke.Although the underlying disorder can be diagnosed after careful medical,neurological,and radiological examinations,a few conditions,such as Wernicke encephalopathy(WE),may present a particular diagnostic difficulty.WE is a neurological disorder caused by deficiency of thiamine(B1 vitamin),most often resulting from alcoholism,malnutrition,hyperemesis gravidarum or bariatric surgery.The diagnosis of WE in a certain historical,clinical setting is easily suggested,but in a few cases presenting with acute neurological deficits,it can be particularly challenging.CASE SUMMARY We present the case of a 63-year-old man who was brought to the emergency department after developing weakness of the left extremities,dizziness and a confusional state,which had lasted for approximately 30 minutes.The patient had a similar episode of a confusional state approximately two months earlier;at that time,a transient ischemic attack was suspected and he was started on aspirin.The initial clinical evaluation and imaging findings were unremarkable for stroke,but the patient’s symptoms,history of chronic alcohol abuse and abnormal liver function tests prompted the consideration of WE.Magnetic resonance imaging findings in subthalamic areas and electroencephalogram data of diffuse delta activity supported this diagnosis.CONCLUSION Through this case report,we aim to underscore the importance of considering WE as a differential diagnosis in patients presenting with symptoms suggestive of stroke,especially when the presentation is atypical or when risk factors for thiamine deficiency are present.Since intravenous thiamine significantly improves outcomes,delayed recognition and treatment in some cases might be deleterious.展开更多
Wernicke encephalopathy(WE) is an acute neurological disorder resulting from vitamin B1 deficiency, which is common in chronic alcoholism and is rare in acute liver failure. So far, there are 2 cases of WE reported af...Wernicke encephalopathy(WE) is an acute neurological disorder resulting from vitamin B1 deficiency, which is common in chronic alcoholism and is rare in acute liver failure. So far, there are 2 cases of WE reported after liver transplantation. Here, we report a case of a 45-year-old nonalcoholic male patient who developed psychiatric and neurological disturbance 15 d after receiving orthotopic liver transplantation because of hepatitis B-related cirrhosis and portal hypertension. Brain magnetic resonance imaging(MRI) showed symmetric high-signal intensities in the periaqueductal area. The patient was diagnosed with WE and given intravenous high-dose vitamin B1 immediately. His neurological disturbance resolved in 7 d after receiving the vitamin B1. Brain MRI after 5 mo showed nearly complete recovery. Most WE cases may be misdiagnosed in patients after liver transplantation, and we should pay more attention to its onset.展开更多
BACKGROUND, Wernicke encephalopathy is a rare but potentially fatal adverse event caused by thiamine deficiency. Reports of non-alcoholic Wernicke encephalopathy due to malignancy are scarce in the literature, with th...BACKGROUND, Wernicke encephalopathy is a rare but potentially fatal adverse event caused by thiamine deficiency. Reports of non-alcoholic Wernicke encephalopathy due to malignancy are scarce in the literature, with those reported mainly being on haematological cancer, followed by gastrointestinal cancer. As a result, there is considerable under-recognition and delay in the diagnosis and treatment of Wernicke encephalopathy in oncology departments. To our knowledge, there has been no report of Wernicke encephalopathy in a patient with esophageal cancer while receiving radiotherapy.CASE SUMMARY A 64-year-old man presented to the oncology outpatient clinic with a history of dysphagia for 2 mo, and was diagnosed with locally advanced esophageal squamous cell carcinoma(stage ⅢB). Radiotherapy was initiated to alleviate dysphagia due to malignant esophageal stenosis;however, the patient exhibited consciousness disturbances starting on day 10 of radiotherapy. Brain magnetic resonance imaging indicated the development of Wernicke encephalopathy. Subsequent treatment with thiamine led to rapid improvement in the patient’s neurological symptoms.CONCLUSION Wernicke encephalopathy may develop in non-alcoholic patients undergoing radiotherapy for esophageal cancer. Early diagnosis and sufficient thiamine supplementation during radiotherapy are essential.展开更多
Wernicke encephalopathy （WE） is an acute or subacute neurological syndrome caused by thiamine （Vitamin B 1） deficiency and is usually underestimated in clinical practice. WE is suspected in merely about 6% of non-...Wernicke encephalopathy （WE） is an acute or subacute neurological syndrome caused by thiamine （Vitamin B 1） deficiency and is usually underestimated in clinical practice. WE is suspected in merely about 6% of non-alcoholic patients and one-third of alcoholic patients, Non-alcoholic causes include gastrointestinal surgery and disease, malnutrition, cancer and chemotherapeutic treatments, and long-term parenteral nutrition.However, few cases were reported about WE in patients with tuberculosis. Early diagnosis and medication are vital for the prognosis of this disease.展开更多
文摘Background: Neurodevelopmental abnormalities in fetal alcohol spectrum disorder (FASD) are linked to brain insulin resistance and oxidative stress. However, the role of thiamine deficiency as a distinct or additive factor in the pathogenesis of the neurodevelopmental and metabolic derangements in FASD has not been determined. Methods: Control and ethanol-exposed human PNET2 cerebellar neuronal cells and rat cerebellar slice cultures were treated with vehicle or pyrithiamine (Pyr) to assess independent and additive effects of thiamine deficiency on ethanol-mediated neurotoxicity, mitochondrial dysfunction, insulin resistance, inhibition of neuronal and glial genes, and oxidative stress. Results: Pyr treatments (0 - 200 µM) caused dose-dependent cell loss (Crystal Violet assay) and reduced mitochondrial function (MTT assay) in PNET2 neuronal cultures. Ethanol alone (100 mM) significantly reduced PNET2 neuronal viability, MTT activity, and ATP production. Over the broad dose range of Pyr treatment, ethanol significantly reduced ATP content and cell number and increased mitochondrial mass (MitoTracker Green). Ex vivo cerebellar slice culture studies revealed ethanol-induced developmental architectural disruption that was substantially worsened by Pyr. The adverse effects of ethanol were linked to increased lipid peroxidation and inhibition of asparatyl-asparaginyl-β-hydroxylase (ASPH) expression. The independent and additive effects of Pyr were associated with increased cytotoxicity, lipid peroxidation, Caspase 3 activation, and Tau accumulation. Conclusions: During development, alcohol exposure and thiamine deficiency exert distinct but overlapping molecular pathologies that ultimately impair the structure and function of cerebellar neurons. While both insults drive cell loss and mitochondrial dysfunction with increased lipid peroxidation, ethanol’s additional inhibitory effects on ASPH reflect impairments in insulin and IGF signaling. In contrast, Pyr’s main adverse effects were likely due to neurotoxicity and the activation of apoptosis cascades. The findings suggest that FASD severity may be reduced by thiamine supplementation, but without additional support for insulin/IGF signaling networks, FASD would not be prevented.
文摘BACKGROUND Several conditions may present with acute neurological symptoms,thus mimicking the presentation of stroke.Although the underlying disorder can be diagnosed after careful medical,neurological,and radiological examinations,a few conditions,such as Wernicke encephalopathy(WE),may present a particular diagnostic difficulty.WE is a neurological disorder caused by deficiency of thiamine(B1 vitamin),most often resulting from alcoholism,malnutrition,hyperemesis gravidarum or bariatric surgery.The diagnosis of WE in a certain historical,clinical setting is easily suggested,but in a few cases presenting with acute neurological deficits,it can be particularly challenging.CASE SUMMARY We present the case of a 63-year-old man who was brought to the emergency department after developing weakness of the left extremities,dizziness and a confusional state,which had lasted for approximately 30 minutes.The patient had a similar episode of a confusional state approximately two months earlier;at that time,a transient ischemic attack was suspected and he was started on aspirin.The initial clinical evaluation and imaging findings were unremarkable for stroke,but the patient’s symptoms,history of chronic alcohol abuse and abnormal liver function tests prompted the consideration of WE.Magnetic resonance imaging findings in subthalamic areas and electroencephalogram data of diffuse delta activity supported this diagnosis.CONCLUSION Through this case report,we aim to underscore the importance of considering WE as a differential diagnosis in patients presenting with symptoms suggestive of stroke,especially when the presentation is atypical or when risk factors for thiamine deficiency are present.Since intravenous thiamine significantly improves outcomes,delayed recognition and treatment in some cases might be deleterious.
基金Supported by National Natural Science Foundation of China,No.81200326Natural Science Foundation of Hunan Province,No.2016JJ3165
文摘Wernicke encephalopathy(WE) is an acute neurological disorder resulting from vitamin B1 deficiency, which is common in chronic alcoholism and is rare in acute liver failure. So far, there are 2 cases of WE reported after liver transplantation. Here, we report a case of a 45-year-old nonalcoholic male patient who developed psychiatric and neurological disturbance 15 d after receiving orthotopic liver transplantation because of hepatitis B-related cirrhosis and portal hypertension. Brain magnetic resonance imaging(MRI) showed symmetric high-signal intensities in the periaqueductal area. The patient was diagnosed with WE and given intravenous high-dose vitamin B1 immediately. His neurological disturbance resolved in 7 d after receiving the vitamin B1. Brain MRI after 5 mo showed nearly complete recovery. Most WE cases may be misdiagnosed in patients after liver transplantation, and we should pay more attention to its onset.
基金Supported by the Scientific Technology Plan Program for Healthcare in Zhejiang Province,No.2021KY1100the Key Discipline of Jiaxing General Practice Medicine Construction Project,No.2019-fc-03.
文摘BACKGROUND, Wernicke encephalopathy is a rare but potentially fatal adverse event caused by thiamine deficiency. Reports of non-alcoholic Wernicke encephalopathy due to malignancy are scarce in the literature, with those reported mainly being on haematological cancer, followed by gastrointestinal cancer. As a result, there is considerable under-recognition and delay in the diagnosis and treatment of Wernicke encephalopathy in oncology departments. To our knowledge, there has been no report of Wernicke encephalopathy in a patient with esophageal cancer while receiving radiotherapy.CASE SUMMARY A 64-year-old man presented to the oncology outpatient clinic with a history of dysphagia for 2 mo, and was diagnosed with locally advanced esophageal squamous cell carcinoma(stage ⅢB). Radiotherapy was initiated to alleviate dysphagia due to malignant esophageal stenosis;however, the patient exhibited consciousness disturbances starting on day 10 of radiotherapy. Brain magnetic resonance imaging indicated the development of Wernicke encephalopathy. Subsequent treatment with thiamine led to rapid improvement in the patient’s neurological symptoms.CONCLUSION Wernicke encephalopathy may develop in non-alcoholic patients undergoing radiotherapy for esophageal cancer. Early diagnosis and sufficient thiamine supplementation during radiotherapy are essential.
文摘Wernicke encephalopathy （WE） is an acute or subacute neurological syndrome caused by thiamine （Vitamin B 1） deficiency and is usually underestimated in clinical practice. WE is suspected in merely about 6% of non-alcoholic patients and one-third of alcoholic patients, Non-alcoholic causes include gastrointestinal surgery and disease, malnutrition, cancer and chemotherapeutic treatments, and long-term parenteral nutrition.However, few cases were reported about WE in patients with tuberculosis. Early diagnosis and medication are vital for the prognosis of this disease.
